Age-related differences in metabolism and blood flow of frontal cortex were enhanced when young and old subjects received sensory activation. A patient with isolated memory impairment and family history for autosomal dominant AD was studied with PET twice and found to have normal glucose metabolism with routine analysis but both scans were found to be abnormal using a discriminant function analysis. Dorsal vs. ventral patterns of regional cerebral blood flow activation during face and location matching were similar in young and old subjects, but were less functionally distinct in older subjects. Activation of regional cerebral blood flow in occipitotemporal cortex was equivalent during face perception in DAT patients and controls; patients also had frontal activation. Patients with late onset depression had increased brain metabolism in orbitofrontal cortex. A patient with autopsy proven Parkinson's disease had a metabolic pattern indistinguishable from that seen in DAT. Patients with vascular dementia had decreased subcortical glucose metabolism compared to DAT patients. Density of neurofibrillary tangles, but not senile plaques in postmortem brain, was correlated with metabolic reductions. A nonretarded patient with mosaic translocation trisomy 21 had cognitive and metabolic impairments typical of DAT suggesting that genetic determinants of dementia in Down syndrome differ from those responsible for retardation. Patients with trichotillomania, a disease similar to obsessive-compulsive disorder, had higher glucose metabolic rates than to controls.